苦马豆素诱导人胃癌细胞SGC-7901凋亡作用机制的实验研究  

Effects of swainsonine on apoptosis of the human gastric carcinoma cell SGC-7901

作　　者：孙纪元[1] 朱妙章[2] 王四旺[1] 谢艳华[1] 缪珊[1] 朱肖星[3] 施新猷[1] 

机构地区：[1]第四军医大学药物研究所,西安710033 [2]第四军医大学生理教研室,西安710033 [3]第四军医大学药理教研室,西安710033

出　　处：《中国新药杂志》2006年第3期197-201,共5页Chinese Journal of New Drugs

摘　　要：目的:探讨苦马豆素(swainsonine,SW)体外诱导人胃癌细胞株SGC-7901凋亡的机制。方法:应用MTT法确定SW对体外培养的SGC-7901细胞的作用浓度;通过流式细胞术及凋亡相关调控基因p53,c-myc,Bcl-2的检测对细胞凋亡及细胞周期的测定,观察SW对胃癌细胞SGC-7901增殖周期的影响以及抑制肿瘤细胞增殖的方式;同时利用激光共聚焦显微镜监测细胞内Ca^(2+)浓度,研究SW与细胞内Ca^(2+)超载的关系。结果:SW体外抗SGC-7901细胞的完全致死浓度为6．2μg·mL^(-1),高于0．05μg·mL^(-1)时抑制作用明显(P＜0．05),其IC_(50)为0．84μg·mL～(-1);经SW 0．5,1．5,4．5μg·mL^(-1)处理24h可引起凋亡抑制基因p53和Bcl-2的明显下降,凋亡促进基因c-myc明显升高以及肿瘤细胞内Ca^(2+)超载,最终诱导SGC-7901细胞凋亡。实验还证实SW主要作用于肿瘤细胞的S期,使瘤细胞主要积聚在S期。结论:SW通过多种途径诱导细胞凋亡可能是其发挥抗癌作用的重要机制。Objective ： To investigate the cell SGC-7901 in vitro by swainsonine. Methods： apoptotic mechanism of the human gastric carcinoma After the cultures of the cell SGC-7901 with a series of concentrations of swainsonine, the ratio of dose-inhibition （IC50） of swainsonine to the cell SGC-7901 were examined by MTT assay. The cell cycle distribution and apoptotic rates were analyzed by flow cytometry. Expression of p53, c-myc and Bcl-2 was assayed using an immunocytochemical method. The concentration of intracellular calcium （ [ Ca^2＋ ]i） was measured by laser scanning confocal microscope （LSCM）. Results：Swainsonine at the concentration 0.05μg·mL^-1 or up significantly inhibited the cell growth of SGC-7901 in vitro with an IC50 0.84 μg·mL^-1 and at 6.2 μg·mL^-1 resulted to the apoptosis of the cell. At the concentrations of 0.5, 1.5 and 4.5μg·mL^-1, swainsonine decreased the expression of apoptosis-inhibited gene p53 and Bcl-2, increased the apoptosis-triggered gene c-myc, and overloading of [ Ca^2＋ ]i inside of the cell post the 24-hours culture leading to the apoptosis of the cell SGC-7901. Moreover, swainsonine was a S phase-specific cytotoxic agent against the cell SGC-7901. Conclusion： Swainsonine is effective against carcinoma by several apoptotic mechanisms.

关 键 词：苦马豆素 胃癌 凋亡 流式细胞仪 细胞周期 激光共聚焦显微镜 

分 类 号：R735.2[医药卫生—肿瘤] R285.5[医药卫生—临床医学]